Airway smooth muscle cell proliferation: characterization of subpopulations by sensitivity to heparin inhibition.
Growth and maturation state of airway smooth muscle cells (SMCs) are determinants of asthma pathophysiology. Heparin reduces airway SMC proliferation and arterial SMC replication and phenotypic modulation. Distinct arterial SMC subtypes, differing in heparin sensitivity, have been characterized. We assessed the cellular mechanisms underlying the growth and phenotype of heparin-treated canine tracheal myocytes in primary culture. Heparin reduced replication by 40%. Immunoblot assay of myosin, actin, and myosin light chain kinase revealed heparin had no effect on rapid spontaneous phenotypic modulation after the cells were plated. Heparin increased cellular protein and vimentin contents in confluent cultures, suggesting that it may induce hypertrophic growth. Cell cycle analysis revealed that heparin decreased serum-stimulated replicating myocyte number by 40%. Also, G2-M transit was 20% slower for the set of SMCs that proceeded past G1 in the presence of heparin. These data indicate that heparin does not inhibit airway SMC replication by blocking modulation from the contractile state. Moreover, airway smooth muscle is composed of distinct SMC populations differing in mitogen and antiproliferative mediator responsiveness. Identification of functionally divergent subgroups suggests that distinct sets of SMCs may contribute differentially to airway physiology and pathophysiology.
Halayko
A J
AJ
Department of Physiology, University of Manitoba, Winnipeg, Canada.
Rector
E
E
Stephens
N L
NL
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D004247:DNA / Q000032:analysis; D004285:Dogs; D005434:Flow Cytometry; D006493:Heparin / Q000494:pharmacology*; D007700:Kinetics; D009130:Muscle, Smooth / Q000166:cytology* / Q000187:drug effects; D014132:Trachea / Q000166:cytology* / Q000187:drug effects
D003470:Culture Media; D006493:Heparin; D004247:DNA